Multimode analytical instruments, also referred to as multimode readers, are apparatus that can perform multiple analytical assays in a single instrument. Standard multimode readers, used within the life science industry, can measure the most common types of assays (i.e., applications, such as fluorescence, luminescence, and absorbance) in a single instrument. The use of a single instrument to perform these assays is advantageous over using multiple dedicated instruments to perform the same measurements. This lies in the fact that a multimode reader can provide ease of use, a better price performance ratio, and require less bench top area than multiple instruments.
Generally, these instruments have built-in general purpose (i.e., white) light sources, such as halogen lamps and xenon flash lamps, and general purpose detectors such as photomultiplier tubes (PMTs) and silicon photodiodes. The instruments also typically include optical filters mounted into wheels or slides, and application specific beamsplitters installed into slides, or into revolver like mechanisms. Multimode readers may also combine filter-based and monochromator-based technology. While components are configured to perform a variety of types of assays, expanding the multimode reader to perform new assays and new applications was often difficult. From a hardware point of view, specific applications may involve accessing a multitude of driven stages for selecting the correct combination and adjustment of filters, beamsplitters, apertures, and lightguides, for example. In these devices, enabling new applications of a given technology required retrofitting specific optical filters and beamsplitters. Adding new applications often required substantial redesign.
In some example implementations, standardized cartridges having a standard form and shape may be configured with components arranged for specific applications, or types of applications. Such cartridges substantially reduce the amount of redesign and retrofitting involved in adding applications. However, with the exception of applications that employ absorbance-based measurements, the advantages have largely been realized for filter-based technologies.
It would be desirable for a multimode reader to fully use both filter-based and monochromator-based technologies. Such a multimode reader would be capable of using a PMT in the photon counting mode and of performing dynamic extension via light level control of the source light (i.e. the LEDs). Such a reader would also be capable of measurements in the analog mode where a Xenon flash lamp light source is used in combination with a monochromator. The flash duration involved with a Xenon flash lamp is typically in the single micro second range. This range of flash duration is too short to permit the use of photon counting for a measurement.
One way to perform dynamic signal extension with a PMT in analog mode is to control the signal output of the source light, which is, as an example, a Xenon flash lamp. Control of the Xenon flash lamp output is difficult, but the main problem with this solution is that it would require a change to the hardware. The control over the output signal level of the PMT may also require discharge capacitors at substantially high power levels. Switching to different levels may not be sufficiently fast enough to address the too short flash duration.
Dynamic extension may also be achieved by varying the gain level of the PMT. In applications that use a flash lamp in combination with a monochromator, the gain level of the PMT cannot be changed quickly enough for the one or several microsecond flash duration. In addition, the gain level of the PMT is not a linear attribute of a PMT. This makes the change of the gain difficult to factor into the result.
The dynamic range of a PMT in analog mode with a constant gain setting is relatively limited to a range of about 5 logs or less. This is too small in some applications where a dynamic range of several times more than 5 logs is needed. Some form of dynamic extension is needed to measure over the full range of the applications.
There is a need in the art for an analytical system that permits variably fast adjustment of the light source output and of the dynamic range of the signal measurement.